Diagnostic Performance of Universal versus Stratified Computer-Aided Detection Thresholds for Chest X-Ray-Based Tuberculosis Screening.

Background: Computer-aided detection (CAD) software analyzes chest X-rays for features suggestive of tuberculosis (TB) and provides a numeric abnormality score. However, estimates of CAD accuracy for TB screening are hindered by the lack of confirmatory data among people with lower CAD scores, including those without symptoms. Additionally, the appropriate CAD score thresholds for obtaining further testing may vary according to population and client characteristics.

Methods: We screened for TB in Ugandan individuals aged ≥15 years using portable chest X-rays with CAD (qXR v3). Participants were offered screening regardless of their symptoms. Those with X-ray scores above a threshold of 0.1 (range, 0 - 1) were asked to provide sputum for Xpert Ultra testing. We estimated the diagnostic accuracy of CAD for detecting Xpert-positive TB when using the same threshold for all individuals (under different assumptions about TB prevalence among people with X-ray scores <0.1), and compared this estimate to age- and/or sex-stratified approaches.

Findings: Of 52,835 participants screened for TB using CAD, 8,949 (16.9%) had X-ray scores ≥0.1. Of 7,219 participants with valid Xpert Ultra results, 382 (5.3%) were Xpert-positive, including 81 with trace results. Assuming 0.1% of participants with X-ray scores <0.1 would have been Xpert-positive if tested, qXR had an estimated AUC of 0.920 (95% confidence interval 0.898-0.941) for Xpert-positive TB. Stratifying CAD thresholds according to age and sex improved accuracy; for example, at 96.1% specificity, estimated sensitivity was 75.0% for a universal threshold (of ≥0.65) versus 76.9% for thresholds stratified by age and sex (p=0.046).

Interpretation: The accuracy of CAD for TB screening among all screening participants, including those without symptoms or abnormal chest X-rays, is higher than previously estimated. Stratifying CAD thresholds based on client characteristics such as age and sex could further improve accuracy, enabling a more effective and personalized approach to TB screening.

Funding: National Institutes of Health.

Research in context: Evidence before this study: The World Health Organization (WHO) has endorsed computer-aided detection (CAD) as a screening tool for tuberculosis (TB), but the appropriate CAD score that triggers further diagnostic evaluation for tuberculosis varies by population. The WHO recommends determining the appropriate CAD threshold for specific settings and population and considering unique thresholds for specific populations, including older age groups, among whom CAD may perform poorly. We performed a PubMed literature search for articles published until September 9, 2024, using the search terms "tuberculosis" AND ("computer-aided detection" OR "computer aided detection" OR "CAD" OR "computer-aided reading" OR "computer aided reading" OR "artificial intelligence"), which resulted in 704 articles. Among them, we identified studies that evaluated the performance of CAD for tuberculosis screening and additionally reviewed relevant references. Most prior studies reported area under the curves (AUC) ranging from 0.76 to 0.88 but limited their evaluations to individuals with symptoms or abnormal chest X-rays. Some prior studies identified subgroups (including older individuals and people with prior TB) among whom CAD had lower-than-average AUCs, and authors discussed how the prevalence of such characteristics could affect the optimal value of a population-wide CAD threshold; however, none estimated the accuracy that could be gained with adjusting CAD thresholds between individuals based on personal characteristics.Added value of this study: In this study, all consenting individuals in a high-prevalence setting were offered chest X-ray screening, regardless of symptoms, if they were ≥15 years old, not pregnant, and not on TB treatment. A very low CAD score cutoff (qXR v3 score of 0.1 on a 0-1 scale) was used to select individuals for confirmatory sputum molecular testing, enabling the detection of radiographically mild forms of TB and facilitating comparisons of diagnostic accuracy at different CAD thresholds. With this more expansive, symptom-neutral evaluation of CAD, we estimated an AUC of 0.920, and we found that the qXR v3 threshold needed to decrease to under 0.1 to meet the WHO target product profile goal of ≥90% sensitivity and ≥70% specificity. Compared to using the same thresholds for all participants, adjusting CAD thresholds by age and sex strata resulted in a 1 to 2% increase in sensitivity without affecting specificity.Implications of all the available evidence: To obtain high sensitivity with CAD screening in high-prevalence settings, low score thresholds may be needed. However, countries with a high burden of TB often do not have sufficient resources to test all individuals above a low threshold. In such settings, adjusting CAD thresholds based on individual characteristics associated with TB prevalence (e.g., male sex) and those associated with false-positive X-ray results (e.g., old age) can potentially improve the efficiency of TB screening programs.